Tocilizumab Group Research Articles

Treatment efficacy and safety of adalimumab versus tocilizumab in patients with active and severe Takayasu arteritis: an open-label study.

This study aimed to compare the efficacy and safety of adalimumab (ADA) vs tocilizumab (TCZ) in patients with Takayasu arteritis (TAK). This was a randomized, controlled, open-label study. Forty patients with active and severe TAK were enrolled. They were treated with ADA (n = 21) combined with glucocorticoids (GCs) and MTX or TCZ (n = 19) combined with GCs and MTX. The planned follow-up duration was 12 months. The primary end point was the efficacy rate (ER) at 6 months. The secondary end points included ER at 9 and 12 months, relapse rate, GC tapering, adverse effects, and life quality changes during treatment. In the intention-to-treat (ITT) population, the ER at 6 months was higher in the ADA group (85.71% vs 52.63%, P = 0.02). A similar direction of effect was noted in the per-protocol set (89.47% vs 62.50%, P = 0.06). The percentages of patients who achieved a GC dose of ≤10 mg/day at 6 months were similar between the ADA and TCZ groups (47.37% vs 43.75%, P = 0.83). The ERs at 9 and 12 months were similar between the two groups (P > 0.05). During the first 12 months of treatment, the relapse rate and adverse event incidence were comparable between the two groups (ADA vs TCZ: 9.52% vs 10.53%, P = 0.96; 38.10% vs 47.37%, P = 0.55, respectively). ADA combined with GCs and MTX may be more efficacious than TCZ combined with GCs and MTX among patients with active and severe TAK. Clinicaltrials.gov; NCT04300686.

Cytokine pattern in patients with ST-elevation myocardial infarction treated with the interleukin-6 receptor antagonist tocilizumab

BackgroundTocilizumab improves myocardial salvage index (MSI) in patients with ST-elevation myocardial infarction (STEMI), but its mechanisms of action are unclear. Here, we explored how cytokines were affected by tocilizumab and...

ВЛИЯНИЕ ГЕМОСОРБЦИИ С ЭКCТРАКОРПОРАЛЬНОЙ АУТОГЕМОМАГНИТОТЕРАПИЕЙ В СРАВНЕНИИ С МЕДИКАМЕНТОЗНОЙ ТЕРАПИЕЙ АНТАГОНИСТАМИ РЕЦЕПТОРОВ ИЛ-6 НА КЛИНИКО-ЛАБОРАТОРНЫЕ ПАРАМЕТРЫ ПАЦИЕНТОВ С ТЯЖЕЛЫМ ТЕЧЕНИЕМ COVID-19

Background: SARS-CoV-2 infection in 10-20% of cases is characterized by hypercytokinemia, and in this context, the use of interleukin-6 (IL-6) receptor blockers, in particular tocilizumab and levilimab, is pathogenetically justified, but anticytokine hemosorption is also used in such cases. It is impossible to determine which method is preferable in patients with severe COVID-19 due to the lack of large comparative studies of medical and extracorporeal anticytokine therapies. Purpose: To evaluate the effect of hemosorption through the Нemo-Рroteasosorb hemorosorbent in combination with extracorporeal autohemomagnetic therapy and medical therapy with IL-6 receptor antagonists on the respiratory status, hemostasis, acid-base state of the blood, the detoxification function of the liver and kidneys in patients with severe COVID-19 infection. Material and methods: The clinical and laboratory findings of 102 patients with a severe course of coronavirus infection, who developed cytokine storm, were evaluated. All patients were divided into three groups: hemosorption with magnetic blood treatment («HS+MBT») (41 patients), Tocilizumab group (40 patients) and Levilimab group (20 patients). The following indicators were studied: erythrocyte count and platelet count; hemoglobin level; concentration of total protein, creatinine, urea, total bilirubin, aspartate aminotransferase (AST), alanine aminotransferase (ALT), fibrinogen, D-dimers; acid-base state and blood gas composition. To assess the respiratory status, the respiratory index (RI), ROX index, total oxygen flow, and dynamics of the level of respiratory support were evaluated. To assess hemodynamics, mean arterial pressure and heart rate were determined, the body temperature of the patients was also measured. Results: The results obtained demonstrate that with the combined use of MBT and hemosorption through the Hemo-Proteasosorb sorbent in patients with severe COVID-19, there were no significant fluctuations in hemodynamic parameters, levels of urea, creatinine, total bilirubin, AST and ALT. At the same time, the use of tocilizumab was associated with an increase in the levels of urea, total bilirubin and ALT. In the Levilimab group there was an increase in the concentration of urea. The use of HS+MBT was associated with a decrease in the level of fibrinogen, which was noted on the next day, as well as a tendency to a decrease in D-dimers. At the same time, during the treatment with IL-6 receptor blockers, a significant decrease in the level of fibrinogen was noted only on days 6-8. The number of thromboembolic complications was also lower in the patients with extracorporeal detoxification. With HS+MBT, an increase in the respiratory status indicators (RI, ROX-index, decrease in total oxygen flow) was observed already on the next day, while in the Tocilizumab and Levilimab groups, an increase in these indicators was noted only on days 6-8. A decrease in the ROX index and the absence of dynamics in the total oxygen flow were found on the next day in both groups. In the HS+MBT group, the obtained results indicated that the given technique both prevents more significantly the transition to the next level of respiratory support and contributes to its decrease as compared to IL-6 receptor blockers. Analysis of the acid-base state of the blood following HS + MBT showed a decrease in the level of lactate and an increase in HCO3, as well as deficiency/excess of bases, which indicated compensation for metabolic acidosis. Similar results with the use of IL-6 receptor blockers were obtained only on the 6th-8th day of the study, but no normalization of the lactate concentration in the blood of patients was found at any stage. Conclusion: The use of HS+MBT has a number of advantages over the treatment with IL-6 receptor blockers, which is manifested by the absence of cardio, hepato- and nephrotoxicity, as well as more significant positive effect on hemostasis, respiratory status and acid-base status of patients.

#3440 TOCILIZUMAB INDUCTION THERAPY IN KIDNEY TRANSPLANTATION

Abstract Background and Aims Antibody induction therapy is frequently used as an adjunct to the maintenance immunosuppression in adult kidney transplant recipients (KTRs). There are few comparisons of antibody induction therapy allowing early glucocorticoid withdrawal in KTRs. The purpose of the present study was to compare induction therapy involving tocilizumab with the most commonly used induction regimens in patient populations at either high immunologic risk or low immunologic risk. Method In this prospective study, we randomly assigned patients to receive tocilizumab or conventional induction therapy such as basiliximab. Patients were stratified according to acute rejection risk, with a high risk defined by a repeat transplant, a peak or current value of panel-reactive antibodies of 30% or more. The 102 high-risk patients received tocilizumab (one dose of 8 mg/kg, in 52 patients) or basiliximab (a total of 40 mg over 4 days, in 50 patients). The 113 low-risk patients received tocilizumab (one dose of 8 mg/kg, in 62 patients) or basiliximab (a total of 40 mg over 4 days, in 51 patients). All patients received tacrolimus and mycophenolate mofetil and underwent a 10-days glucocorticoid (prednisone) taper in a regimen of early steroid withdrawal. The primary end point was biopsy-confirmed acute rejection at 6 months and 12 months. Patients were followed for 2 years for safety and efficacy end points. Results The rate of biopsy-confirmed acute rejection was significantly lower in the tocilizumab group than in the basiliximab group at both 6 months (5.3% vs. 10.9%, P<0.01) and 12 months (7.9% vs. 12.9%, P<0.01). At 2 years, the rate of biopsy-confirmed acute rejection in low-risk patients was lower with tocilizumab than with basiliximab (9.7% vs. 17.7%, P<0.05), but among high-risk patients, no significant difference was seen between tocilizumab and basiliximab (19.2% vs. 16.0%, P = 0.68). Adverse-event rates were similar among all four treatment groups. Conclusion By the first year after transplantation, biopsy-confirmed acute rejection was less frequent with tocilizumab than with conventional therapy. The apparent superiority of tocilizumab with respect to early biopsy-confirmed acute rejection was restricted to patients at low risk for transplant rejection; among high-risk patients, tocilizumab and basiliximab had similar efficacy. Further randomized and controlled studies are needed to support these results.

Tocilizumab suppresses NF-kappa B activation via toll-like receptor 9 signaling by reducing cell-free DNA in rheumatoid arthritis.

Endogenous DNA is released into the bloodstream as cell-free DNA (cfDNA) following cell death and is associated with various pathological conditions. However, their association with therapeutic drugs against rheumatoid arthritis (RA) remains unknown. Therefore, we investigated the significance of cfDNA in RA treated with tocilizumab and tumour necrosis factor inhibitor (TNF-I). Biological DMARDs (bDMARDs), including tocilizumab and TNF-I, were administered to 77 and 59 RA patients, respectively. Plasma cfDNA levels were measured at weeks 0, 4, and 12 by quantitative polymerase chain reaction. Disease activity was evaluated at the same time point using DAS28ESR. cfDNA levels from RA synovial cells treated with tocilizumab or etanercept for 24 h were measured. Human toll-like receptor 9 (hTLR9)-expressing HEK293 cells, which release secreted embryonic alkaline phosphatase (SEAP) upon NF-κB activation, were stimulated by cfDNA from RA patients, and subsequently, SEAP levels were determined. NF-κB translocation was evaluated by immunofluorescence staining with or without tocilizumab. The DAS28ESR significantly improved in both bDMARD groups at week 12. However, plasma cfDNA levels significantly decreased in the tocilizumab group at week 12 compared to that in week 0. cfDNA levels correlated with DAS28ESR in biological treatment-naïve patients administered tocilizumab. cfDNA levels in synovial cells were significantly suppressed by tocilizumab treatment and unaltered with etanercept. HEK293 cells released SEAP upon cfDNA stimulation, and the observed NF-κB nuclear translocation was suppressed by tocilizumab. Tocilizumab suppressed inflammation via the TLR9 pathway by decreasing cfDNA levels. Regulation of cfDNA may be a therapeutic target for RA.

Tocilizumab versus anakinra in COVID-19: results from propensity score matching.

Tocilizumab and anakinra are anti-interleukin drugs to treat severe coronavirus disease 2019 (COVID-19) refractory to corticosteroids. However, no studies compared the efficacy of tocilizumab versus anakinra to guide the choice of the therapy in clinical practice. We aimed to compare the outcomes of COVID-19 patients treated with tocilizumab or anakinra. Our retrospective study was conducted in three French university hospitals between February 2021 and February 2022 and included all the consecutive hospitalized patients with a laboratory-confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection assessed by RT-PCR who were treated with tocilizumab or anakinra. A propensity score matching was performed to minimize confounding effects due to the non-random allocation. Among 235 patients (mean age, 72 years; 60.9% of male patients), the 28-day mortality (29.4% vs. 31.2%, p = 0.76), the in-hospital mortality (31.7% vs. 33.0%, p = 0.83), the high-flow oxygen requirement (17.5% vs. 18.3%, p = 0.86), the intensive care unit admission rate (30.8% vs. 22.2%, p = 0.30), and the mechanical ventilation rate (15.4% vs. 11.1%, p = 0.50) were similar in patients receiving tocilizumab and those receiving anakinra. After propensity score matching, the 28-day mortality (29.1% vs. 30.4%, p = 1) and the rate of high-flow oxygen requirement (10.1% vs. 21.5%, p = 0.081) did not differ between patients receiving tocilizumab or anakinra. Secondary infection rates were similar between the tocilizumab and anakinra groups (6.3% vs. 9.2%, p = 0.44). Our study showed comparable efficacy and safety profiles of tocilizumab and anakinra to treat severe COVID-19.

Effectiveness of tocilizumab in non-intubated cases with COVID-19: a systematic review and meta-analysis.

Tocilizumab, a monoclonal IL-6 receptor blocker, is an effective agent for severe-to-critical cases of COVID-19; however, its target patients for the optimum use need to be detailed. We performed a systematic review and meta-analysis to define its effect among severely ill but non-intubated cases with COVID-19. We searched PubMed, Scopus, Web of Science, MEDLINE, Cochrane Central Register of Controlled Trials (CENTRAL), Medrxiv, and Biorxiv until February 13, 2022, for non-intubated cases, and included randomized-controlled trials (RCT) based on bias assessment. The primary outcomes were the requirement of invasive mechanical ventilation and mortality. Random effect and fixed-effect models were used. The heterogeneity was measured using the χ2 and I2 statistics, with χ2 p ≤ 0.05 and I2 ≥ 50% indicating the presence of significant heterogeneity. We registered the study to the International Prospective Register of Systematic Reviews (PROSPERO) with the registration number CRD42021232575. Among 261 articles, 11 RCTs were included. The pooled analysis of the 11 RCTs demonstrated that the rate of mortality was significantly lower in the tocilizumab group than in the control group (20.0% and 24.2%, OR: 0.84, 95% CI 0.73-0.96, and heterogeneity I2 = 0%. p = 0.82.). The mechanical ventilation rate was lower in the tocilizumab group than the control group (27% vs 35.2%, OR: 0.76, 95% CI 0.67-0.86, and heterogeneity I2 = 6%. p = 0.39). Among non-intubated severe COVID-19 cases, tocilizumab reduces the risk of invasive mechanical ventilation and mortality compared to standard-of-care treatment.

Development of a New Analytical Method for Estimation of Trifluoperazine-HCl in Pharmaceutical Formulation

Background: Coronavirus disease 2019 (COVID-19) has spread worldwide and poses a serious public health-threat. High IL-6 levels were associated with the severity of COVID-19 and del to the use of anti-IL-6 Tocilizumab during the pandemic. Therefore, this case-control study was conducted to evaluate the role of Tocilizumab on the mortality rate among severe and critically ill COVID-19 patients. Method: A case-control study relied on the use of an electronic data collection sheet; the data were collected from February to May 2022. The study was performed on adult patients with critical COVID-19 at three major hospitals in the Gaza Strip, Palestine where patients were treated in the intensive care units (ICUs). Patients from the hospitals were included and divided into two groups by simple random sampling technique. Results: Of the 202 patients with critical COVID-19 admitted to ICUs of three hospitals, 102 (50.5%) were treated with Tocilizumab. A total of 58 (56.9%) patients in the Tocilizumab group were cured, and 44 (43.1%) died. In the control group, only 26 (26.0%) were cured and 72.0% died. There was no statistically significant effect of Tocilizumab on total hospital stay and ventilation periods. Patients treated with Tocilizumab had a longer stay in the ICU (14.02 ±8.796 days compared to 10.52 ± 9.596 days in the control group, P = 0.027), but shorter incubation periods were observed in the same group (3.25 ±1.137 days in Tocilizumab group compared to 7.38 ±3.376 days in the control group P = 0.036). Conclusion: This study found that administration of Tocilizumab can improve clinical outcomes, reduce risk of mortality, and frequency of intubation in patients severely infected with COVID-19. However, there was no significant difference between the two groups in terms of hospitalization times and mechanical ventilation needs. Based on the current report, healthcare specialists should consider Tocilizumab with the updated treatment guidelines for critically ill COVID-19 patients.

Tocilizumab Outcomes in Critically Ill COVID-19 Patients Admitted to the ICU and the Role of Non-Tocilizumab COVID-19-Specific Medical Therapeutics

Tocilizumab is a monoclonal antibody proposed to manage cytokine release syndrome (CRS) associated with severe COVID-19. Previously published reports have shown that tocilizumab may improve the clinical outcomes of critically ill patients admitted to the ICU. However, no precise data about the role of other medical therapeutics concurrently used for COVID-19 on this outcome have been published. We aimed to compare the overall outcome of critically ill COVID-19 patients admitted to the ICU who received tocilizumab with the outcome of matched patients who did not receive tocilizumab while controlling for other confounders, including medical therapeutics for critically ill patients admitted to ICUs. A prospective, observational, multicenter cohort study was conducted among critically ill COVID-19 patients admitted to the ICU of 14 hospitals in Saudi Arabia between 1 March 2020, and October 31, 2020. Propensity-score matching was utilized to compare patients who received tocilizumab to patients who did not. In addition, the log-rank test was used to compare the 28 day hospital survival of patients who received tocilizumab with those who did not. Then, a multivariate logistic regression analysis of the matched groups was performed to evaluate the impact of the remaining concurrent medical therapeutics that could not be excluded via matching 28 day hospital survival rates. The primary outcome measure was patients' overall 28 day hospital survival, and the secondary outcomes were ICU length of stay and ICU survival to hospital discharge. A total of 1470 unmatched patients were included, of whom 426 received tocilizumab. The total number of propensity-matched patients was 1278. Overall, 28 day hospital survival revealed a significant difference between the unmatched non-tocilizumab group (586; 56.1%) and the tocilizumab group (269; 63.1%) (p-value = 0.016), and this difference increased even more in the propensity-matched analysis between the non-tocilizumab group (466.7; 54.6%) and the tocilizumab group (269; 63.1%) (p-value = 0.005). The matching model successfully matched the two groups' common medical therapeutics used to treat COVID-19. Two medical therapeutics remained significantly different, favoring the tocilizumab group. A multivariate logistic regression was performed for the 28 day hospital survival in the propensity-matched patients. It showed that neither steroids (OR: 1.07 (95% CI: 0.75-1.53)) (p = 0.697) nor favipiravir (OR: 1.08 (95% CI: 0.61-1.9)) (p = 0.799) remained as a predictor for an increase in 28 day survival. The tocilizumab treatment in critically ill COVID-19 patients admitted to the ICU improved the overall 28 day hospital survival, which might not be influenced by the concurrent use of other COVID-19 medical therapeutics, although further research is needed to confirm this.

The effectiveness of Tocilizumab in severe covid 19 pneumonia among critically ill patients

Background: Tocilizumab, an interleukin-6 (IL-6) antagonist, is being evaluated for the management of covid-19 pneumonia. The objective of this study was to assess the effectiveness of Tocilizumab in severe covid-19 pneumonia. Methods: This was a retrospective, observational, single centre study performed in 121 patients diagnosed with severe covid-19 pneumonia. 83 patients received standard of care treatment whereas 38 patients received tocilizumab along with standard of care. Tocilizumab was administered intravenously at 8mg/kg (upto a maximum of 800mg). The second dose of Tocilizumab was given 12 to 24 hours apart. The primary outcome measure was ICU related and hospital related mortality. The secondary outcome measures were change in clinical status of patients measured by WHO (World Health Organisation) 7 category ordinary scale, changes in interleukin-6 (IL-6) levels, secondary infections and duration of ICU stay. Results: Tocilizumab was administered between 3-27 days after the patient reported symptoms ( a median of 10.9 days ) and between the 1st to 3rd day of ICU admission (median of 2.1 days) . In Tocilizumab group, 16(42.1%) of 38 patients died in ICU whereas in standard of care group, 27(32.53%) of 83 patients died. The difference in clinical status assessed using WHO (World Health Organisation) 7 category ordinary scale at 28 days between Tocilizumab group and standard of care group was not statistically significant (odds ratio 1.35, 95% confidence interval 0.61 to 2.97, p = 0.44). Conclusion: Tocilizumab plus standard care was not superior to standard care alone in reducing mortality and improving clinical outcomes at day 28.

Tocilizumab Versus Baricitinib for the Treatment of COVID-19 in Patients With Obesity

Background: Tocilizumab and baricitinib have emerged as potential treatments for patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) following the findings of the Recovery Group and the results of the COV-BARRIER study. Unfortunately, there is a lack of guidance regarding the use of these agents in high-risk patients, such as those with obesity. Objective: To compare the outcomes of tocilizumab and baricitinib as potential treatments for obese patients infected with SARS-CoV-2. Methods: This was a multi-center retrospective analysis comparing outcomes of obese patients who received the standard of care plus tocilizumab or baricitinib for the treatment of SARS-CoV-2. Included patients had a BMI >30 kg/m2, needed ICU level care, and required non-invasive or invasive ventilatory support. Results: This study included 64 patients who received tocilizumab and 69 patients who received baricitinib. When examining the primary outcome, patients who received tocilizumab had a shorter duration of ventilatory support (10.0 vs 15.0 days, P = .016) than patients who received baricitinib. Our secondary outcome of in-hospital mortality was lower in the tocilizumab group as well (23.4% vs 53.6%, P < .001). Tocilizumab was also associated with a non-significant reduction in new positive blood cultures (13.0% vs 3.1%, P = .056) and new invasive fungal infection (7.3% vs 1.6%, P = .210). Conclusions: This retrospective review showed a reduced duration of ventilatory support in obese patients who received tocilizumab vs baricitinib. In the future, additional studies should be conducted to further examine and confirm these results.

A comparison of the effectiveness of different doses of tocilizumab and sarilumab in the treatment of severe COVID-19: a natural experiment due to drug shortages

ObjectivesInterleukin (IL)-6 inhibitors are administered to treat patients hospitalized with COVID-19. In 2021, due to shortages, different dosing regimens of tocilizumab, and a switch to sarilumab, were consecutively implemented. Using real-world data, we compare the effectiveness of these IL-6 inhibitors. MethodsHospitalized patients with COVID-19, treated with IL-6 inhibitors, were included in this natural experiment study. Sixty-day survival, hospital- and intensive care unit (ICU) length of stay, and progression to ICU or death were compared between 8 mg/kg tocilizumab, fixed-dose tocilizumab, low-dose tocilizumab, and fixed-dose sarilumab treatment groups. ResultsA total of 5485 patients from 49 hospitals were included. After correction for confounding, increased hazard ratios (HRs) for 60-day mortality were observed for fixed-dose tocilizumab (HR 1.20, 95% confidence interval [CI] 1.04-1.39), low-dose tocilizumab (HR 1.12, 95% CI 0.97-1.31), and sarilumab (HR 1.24, 95% CI 1.08-1.42), all relative to 8 mg/kg. The 8 mg/kg dosing regimen had lower odds of progression to ICU or death. Both hospital- and ICU length of stay were shorter for low-dose tocilizumab than for the 8 mg/kg group. ConclusionWe found differences in the probability of 60-day survival and the incidence of the combined outcome of mortality or ICU admission, mostly favoring 8 mg/kg tocilizumab. Because of potential time-associated residual confounding, further clinical studies are warranted.

Efficacy and safety of Tocilizumab, plasmapheresis and their combination in severe COVID-19: A randomized clinical trial

This study sought to evaluate and compare the effectiveness of plasmapheresis, Tocilizumab, and Tocilizumab with plasmapheresis treatment on the removal of inflammatory cytokines and improvement clinically of patients with severe COVID-19 in Intensive Care Units (ICU) due to the association between increased cytokine release and the severity of COVID-19. This clinical trial study was conducted in three treatment arms in Iran. All patients received standard care and randomization into one of three treatment groups; Tocilizumab (TCZ) alone, plasmapheresis alone, or a combination of Tocilizumab and plasmapheresis. Demographics, clinical evaluation, oxygenation status, laboratory tests and imaging data were evaluated in the three groups and re-checked 48h after the end of treatment trials. Primary outcomes were oxygenation status, the need for mechanical ventilation and the rate of death. Ninety-four patients were included in the trial after meeting the eligibility requirements. Twenty-eight patients received Tocilizumab alone, 33 had plasmapheresis alone, and 33 received both Tocilizumab and plasmapheresis. Baseline characteristics did not differ between three groups that included demographic, clinical and laboratory parameters. Following therapy, there was no difference between the three groups for CRP, ferritin, d-dimer, IL-6, pro-calcitonin and neutrophil to lymphocyte ratio (NLR) (P>0.05). While a significant reduction was found in CRP levels within each group (32.04±42.43 to 17.40±38.11, 51.28±40.96 to 26.36±33.07 and 41.20±34.27 to 21.56±24.96 in the tocilizumab, plasmapheresis, and combined group, respectively) (p<0.05), procalcitonin levels were elevated significantly in the Tocilizumab group (0.28±0.09 to 0.37±0.11) (p<0.05). Clinically there was no difference between the three groups following treatment for O2 saturation levels with supplementary oxygen at discharge, endotracheal intubation rate, use of NIVPP, mortality, mean hospital and ICU length of stay (p>0.05). Study results showed that the reduction of serum inflammatory markers, the rate of intubation and therapeutic complications including death were no different between the three groups; however, CRP levels were significantly reduced in all three groups, indicating that the interventions reduced inflammation likely through a reduction in the cytokine storm, though clinical outcomes were unaffected.

Possible immuno-modulatory effects of tocilizumab in patients with refractory status epilepticus.

Refractory Status Epilepticus (RSE) is a neurologic emergency that carries a high risk of mortality and morbidity. Every year, there are about 200,000 cases in the United States, affecting people of all ages. This study aimed to investigate the possible immuno-modulatory effect of tocilizumab in RSE patients receiving conventional anti-epileptic drugs. 50 outpatients who fulfilled the inclusion requirements for RSE were recruited in this randomized, controlled, and prospective study. The patients were divided into two groups randomly (n=25); the control group received standard RSE treatment, consisting of propofol, pentobarbital, and midazolam, and the tocilizumab group received standard RSE treatment plus tocilizumab. A neurologist evaluated each patient at the beginning of the therapy and after 3 months. Before and after treatment, serum nuclear factor kappa B (NF-κB), interleukin-6 (IL-6), tumour necrosis factor-alpha (TNF-α), interleukin-1β (IL-1β) and serum electrolytes were assessed. The tocilizumab group showed a statistically significant reduction in the level of assessed parameters in comparison with the control group. Tocilizumab might be a novel adjuvant anti-inflammatory medication in managing RSE.

Experience of using genetically engineered biological drugs in children with a systemic form of JIA in the Karaganda region.

Despite all the achievements of science and medicine, juvenile idiopathic arthritis today remains one of the main childhood diseases that lead to severe irreversible consequences. This, in turn, makes it urgent to search for effective drugs for the treatment of juvenile idiopathic arthritis, of which interleukin 1 (anakinra) and interleukin 6 (tocilizumab) inhibitors are becoming increasingly popular. AIM: to analyse the efficacy of genetically engineered biological drugs, namely anakinra and tocilizumab in children with systemic juvenile idiopathic arthritis among patients of the Karaganda region. The study involved 176 patients aged 4-17 years with a diagnosis of systemic juvenile idiopathic arthritis and with resistance to methotrexate for 3 months. Among all patients, 64 children received injections of anakinra, and 63 received tocilizumab in standard doses. The control group consisted of 50 patients of the same age category. Assessment of the efficacy of treatment was conducted at 2, 4, 8, 16, 24, and 48 weeks using ACR Pediatric criteria. The clinical effect of both drugs was detected as early as the second week after the start of therapy. At week 12 of the study in the tocilizumab group, the efficacy of treatment for ACR Pediatric 30, 50, and 70 reached 82 %, 71 %, and 69 %, and in the anakinra group - 89 %, 81 %, and 80 % respectively, while in the control group ACR Pediatric 30 after 12 weeks of treatment was achieved in 21 % of patients, ACR Pediatric 50 - in 12 %, and ACR Pediatric 70 - in 9 % (p Keywords: systemic arthritis, polyarthritis, tocilizumab, anakinra, genetically engineered biological drugs.

Intravenous Tocilizumab versus Standard of Care in the Treatment of Severe and Critical COVID-19-related Pneumonia: A Single Center, Double-blind, Placebo Controlled, Phase 3 Trial

Background. Severe and critical COVID-19 disease is characterized by hyperinflammation involving pro-inflammatory cytokines, particularly IL-6. Tocilizumab is a monoclonal antibody that blocks IL-6 receptors.Objectives. This study evaluated the efficacy of tocilizumab in Filipino patients with severe to critical COVID-19 disease.&nbsp;Methods. This phase 3 randomized double-blind trial, included patients hospitalized for severe or critical COVID-19 in a 1:1 ratio to receive either tocilizumab plus local standard of care or placebo plus standard of care. Patients were eligible for a repeat IV infusion within 24-48 hours if they deteriorated or did not improve. Treatment success or clinical improvement was defined as at least two categories of improvement from baseline in the WHO 7-point Ordinal Scale of patient status, in an intention-to-treat manner.Results. Forty-nine (49) patients were randomized in the tocilizumab arm and 49 in the placebo arm. There was no significant difference in age, comorbidities, COVID-19 severity, need for mechanical ventilation, presence of acute respiratory distress syndrome, or biomarker levels between groups. Use of adjunctive therapy was similar between groups, with corticosteroid used in 91.8% in tocilizumab group and 81.6% in the placebo group, while remdesivir was used in 98% of participants in both groups.There was no significant difference between groups in terms of treatment success in both the intention-to-treatanalysis (relative risk=1.05, 95% CI: 0.85-1.30) and per-protocol analysis (relative risk=0.98, 95% CI: 0.80 to 1.21).There was no significant difference in time to improvement of at least two categories relative to baseline on the7-point Ordinal Scale of clinical status.Conclusion. The use of tocilizumab on top of standard of care in the management of patients with severe to critical COVID-19 did not result in significant improvement as defined by the WHO 7-point Ordinal Scale of patient status, nor in significant improvement in incidence of mechanical ventilation, incidence of ICU admission, length of ICU stay, and mortality rate.

Modulation of inflammation by treatment with tocilizumab after out-of-hospital cardiac arrest and associations with clinical status, myocardial- and brain injury

AimTo investigate how the inflammatory response after out-of-hospital cardiac arrest (OHCA) is modulated by blocking IL-6-mediated signalling with tocilizumab, and to relate induced changes to clinical status, myocardial- and brain injury. MethodsThis is a preplanned substudy of the IMICA trial (ClinicalTrials.gov, NCT03863015). Upon admission 80 comatose OHCA patients were randomized to infusion of tocilizumab or placebo. Inflammation was characterized by a cytokine assay, CRP, and leukocyte differential count; myocardial injury by TnT and NT-proBNP; brain injury by neuron-specific enolase (NSE) and Neurofilament Light chain (NFL), while sequential organ assessment (SOFA) score and Vasoactive-Inotropic Score (VIS) represented overall clinical status. ResultsResponses for IL-5, IL-6, IL-17, neutrophil as well as monocyte counts, and VIS were affected by tocilizumab treatment (all p < 0.05), while there was no effect on levels of NFL. IL-5 and IL-6 were substantially increased by tocilizumab, while IL-17 was lowered. Neutrophils and monocytes were lower at 24 and 48 hours, and VIS was lower at 24 hours, for the tocilizumab group compared to placebo. Multiple correlations were identified for markers of organ injury and clinical status versus inflammatory markers; this included correlations of neutrophils and monocytes with TnT, NSE, NFL, SOFA- and VIS score for the tocilizumab but not the placebo group. NT-proBNP, NFL and SOFA score correlated with CRP in both groups. ConclusionsTreatment with tocilizumab after OHCA modulated the inflammatory response with notable increases for IL-5, IL-6, and decreases for neutrophils and monocytes, as well as reduced vasopressor and inotropy requirements.

1111. Baricitinib versus Tocilizumab for Hospitalized Adults with Severe COVID-19 in a Community Health System: A Retrospective Cohort

Abstract Background Severe coronavirus disease 2019 (COVID-19) is associated with respiratory failure as well as thromboembolic and cardiovascular complications from dysregulated immune responses. Baricitinib (BAR), a Janus kinase (JAK) inhibitor, and tocilizumab (TZB), a monoclonal anti-interleukin-6 (IL-6) receptor antibody, earned Emergency Use Authorizations (EUA) from the Food and Drug Administration (FDA) for the treatment of COVID-19. This study aims to compare the effects of BAR and TZB in severe COVID-19. Methods A retrospective chart review of patients admitted to Cleveland Clinic Martin Health with COVID-19 having received TZB or BAR was completed between 07/01/20 to 12/31/21. Exclusion criteria included patients who had received both agents in the same admission, received fewer than 5 doses of remdesivir, or were pregnant. The primary objective was to evaluate in-hospital mortality. For secondary outcomes, hospital length of stay (LOS), intensive care unit LOS, readmission due to respiratory-related causes, progression to mechanical ventilation (MV) and CRP levels upon discharge or death were assessed. Safety outcomes were described by incidences of superimposed bacterial infections, thrombosis, and herpes simplex virus reactivation. Results After adjustment of sex and CRP level, the odds of death in TZB was 86% higher than that of BAR group (OR 1.86, 95%CI 1.17-2.96, p=0.009). TZB group had more females (45% vs. 34%, p=0.036) and longer LOS (median [IQR]: 15 [10,23] vs. 13 [9,20], p=0.0390). TZB group had more organ support (47% vs. 29%, p&amp;lt; 0.001), more ICU admission and longer ICU LOS, more MV progression and longer duration of MV (36% vs. 22%, p=0.007; 0[0,9] vs. 0[0,2], p&amp;lt; 0.001). TZB had more additional source of infection (25% vs. 16%, p=0.043) and more positive microbiology from blood (10% vs. 3%, p=0.009). Conclusion Our findings suggest that BAR may have lower rates of in-hospital mortality when compared to TZB. TZB was also found to have higher needs for organ support. Superimposed infections, thrombosis, and HSV reactivation were similar in both groups. Larger randomized studies comparing these agents are needed. Disclosures All Authors: No reported disclosures.

Depression, Anxiety, and Quality of Life in Patients Treated with Single Infusion Tocilizumab for COVID-19: A Follow-up, Controlled Study.

The inflammatory state that characterizes COVID-19 may contribute to depression, anxiety, other morbidities, and mortality. Interleukin-6 blocker tocilizumab has been used as a treatment modality in COVID-19 as an anti-inflammatory agent. Tocilizumab has also been studied for its potential use in preventing depression in other patient groups, with mixed results. This study was designed to study subsequent depression, anxiety, and quality of life (QOL) in patients treated with tocilizumab plus standard care versus standard care alone, for moderate to severe COVID-19 pneumonia. Patients admitted with moderate to severe COVID pneumonia, treated with tocilizumab plus standard treatment, and discharged from the hospital were identified. Age- and gender-matched controls who had received standard treatment alone for COVID-19 pneumonia during the same time frame were identified. After obtaining consent, these patients were followed up and assessed at 3 and 6 months on measures of depression (PHQ-9), anxiety (GAD-7), and QOL (EQ-5D-5L). 39 patients in the tocilizumab group and 41 in the control group were followed up at 3 and 6 months. Patients in both groups were comparable in sociodemographic and clinical parameters. The prevalence of clinically significant depression in the tocilizumab group at 3 and 6 months was 33.33% and 5.12%, respectively, whereas in control group it was 31.7% and 4.87%, respectively. Analysis of EQ-5D health profiles revealed that the maximum problems were reported in the dimension of mobility: 43.7% at 3 months and 35% at 6 months. Depressive and anxiety symptoms and impairment in QOL were reported more frequently and with greater severity in patients in the tocilizumab group at three months but not at six months. Psychological morbidity and impairment in QOL were modest and improved from 3 to 6 months.

Six-month outcomes of infliximab and tocilizumab therapy in non-infectious retinal vasculitis.

To evaluate the efficacy of infliximab (IFX, 5-10 mg/kg) (Group 1) and tocilizumab (TCZ, 4-8 mg/kg) (Group 2) infusions in non-infectious retinal vasculitis (RV) using Angiographic Scoring for the Uveitis Working Group fluorescein angiography (FA) scoring system. Records of 14 patients (24 eyes) in Group 1 and 8 patients (11 eyes) in Group 2 were retrospectively evaluated to assess visual acuity (VA), anterior chamber cell and flare, vitreous haze, central subfield thickness (CST), and FA scoring at baseline and 6 months of follow-up. The measurements were employed to grade in each group. In Group 1 and 2, respectively, there was no underlying disease in 9 (60%) and 3 (42.9%) patients. Three (42.9%) patients in Group 2 had juvenile idiopathic arthritis (JIA) as the most common identified cause. Mean improvement in VA (log MAR) and CST were 0.04 ± 0.14 and 40.3 ± 78.5 µm in Group 1; 0.04 ± 0.09 and 47.3 ± 82.3 µm in Group 2, respectively. Mean FA scores were significantly reduced from 12.4 ± 5.2 and 11.6 ± 4.4 at baseline to 6.4 ± 5.0 and 5.8 ± 3.9 at 6-month in Group 1 and 2, respectively. In Group 2, 9 eyes of 6 patients (75%) had the history of IFX use prior to TCZ initiation. There was no significant safety concern requiring treatment discontinuation during the follow-up in either group. IFX and TCZ infusions showed statistically significant improvement of non-infectious RV as shown by ASUWOG FA Scoring System. TCZ, as well as IFX, appeared to be effective treatment options for non-infectious RV.